Medical antimicrobial composition and medical device comprising the same

ABSTRACT

A medical antimicrobial composition includes a siloxanyl structure-containing polymer and an ammonium group-containing polymer, which is excellent in transparency, flexibility and mechanical properties, and also excellent in adhesion to a base resin with good mechanical properties, particularly to a silicone resin. The medical antimicrobial composition includes an ammonium group-containing polymer compound (A) dispersed in a siloxanyl structure-containing polymer (B) and a medical device comprising the medical antimicrobial composition.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a Continuation application of U.S. patentapplication Ser. No. 12/921,500, filed Sep. 8, 2010, which itself is aNational Phase application of PCT International Application No.PCT/JP2009/054121, filed Mar. 5, 2009, and claims priority to JapanesePatent Application No. 2008-059108, filed Mar. 10, 2008, the contents ofall of these applications being incorporated by reference herein intheir entireties.

FIELD OF THE INVENTION

The present invention relates to a medical antimicrobial composition anda medical device comprising the same.

BACKGROUND OF THE INVENTION

In the medical field, the infectious disease caused while a medicaldevice formed of a polymeric material such as polyurethane is keptinserted or self-retained in the body of a patient is considered aproblem as one of complications. Hitherto, in order to prevent theinfectious disease caused by an indwelling medical device, the medicaldevice is immersed in an aqueous solution containing an antimicrobialagent or disinfectant such as chlorohexidine or povidone iodine fordisinfection immediately before use. As another method, in the casewhere the medical device can be exchanged during treatment, it isfrequently exchanged. However, it is evident that an antimicrobial agentor disinfectant vanishes from the surface of a catheter with the lapseof time and cannot sustain the effect of disinfection and that in thecase where a medical device is used for a long period of time, theeffect of disinfection gradually declines. Further, the frequentexchanges of medical devices impose large burdens on medical workers.Therefore, as means for further prevention of infection, medical devicesare variously processed to be antimicrobial. Typical approaches includecatheters covered on the surfaces with antimicrobial agents such aschlorohexidine and catheters covered on the surfaces with a layercontaining a metal such as silver or copper or a compound thereof. Thesecatheters employ a system in which a material with antimicrobial actionis gradually released at a constant rate in the body of a patient, andshow a good effect compared with the cases where catheters aredisinfected immediately before they are used.

However, a system in which an antimicrobial material is graduallyreleased is still limited in the period of use and cannot avoid that thepotency gradually declines. With regard to metals such as silver andcompounds thereof, the internal kinetics prevailing after they aregradually released is unknown and they may also be harmful to the humanbody. Further, in the case where silver remains in the medical devicewaste after use, any special action of recovering silver from the wasteis necessary.

For these reasons, as an alternative to slowly releasable chemicals,various polymers having ammonium groups are proposed as antimicrobialpolymers (Patent Document 1). However, these polymers cannot be easilyprocessed and cannot be easily molded alone. Therefore, it is proposedthat an article produced by molding a polymer with excellent mechanicalproperties is coated on the surface with any of such antimicrobialpolymers, or that a mixture consisting of an antimicrobial polymer and apolymer with excellent mechanical properties is molded into an article(Patent Documents 2 and 3).

However, a base resin with good mechanical properties, particularly asilicone has a problem that it is poor in adhesion to another polymer,and it is difficult to coat the surface of a silicone with a polymerhaving ammonium groups. Further, there is another problem that if apolymer containing a siloxanyl structure such as a silicone resin ismixed with a polymer having ammonium groups, transparency is impaired. Amaterial mainly composed of a silicone rubber and capable of graduallyreleasing an antimicrobial agent is also known, but it does not solvethe problem of the aforementioned slow-releasing antimicrobial system(Patent Document 4).

Further, document 5 discloses a method comprising the steps ofimpregnating a polymer base with a solution of an alkoxysilane with aquaternary ammonium salt and polycondensing said alkoxysilane in such amanner as to form inter-penetrating networks in said polymer base.However, such formation of alkoxysilane condensation product has aproblem of raising the elastic modulus of the polymer base, fordecreasing the flexibility thereof, and tending to lower the mechanicalproperties of the polymer base as the case may be.

[Patent Document 1] JP 54-17797 B [Patent Document 2] JP 10-081717 A[Patent Document 3] JP 11-99200 A [Patent Document 4] JP 60-80457 A[Patent Document 5] JP 2006-509532 A SUMMARY OF THE INVENTION

The invention provides a medical antimicrobial composition in which anammonium group-containing polymer compound is dispersed in a siloxanylstructure-containing polymer, which is excellent in transparency,flexibility and mechanical properties and also excellent in adhesion toa base resin with good mechanical properties, particularly to a siliconeresin. Additionally, the invention provides a medical device comprisingsaid medical antimicrobial composition.

Embodiments of the invention may have one or more of the followingconfigurations.

[1] A medical antimicrobial composition characterized in that anammonium group-containing polymer compound (A) is dispersed in asiloxanyl structure-containing polymer (B).[2] A medical antimicrobial composition, according to [1] mentionedabove, wherein if the number of hydroxyl groups bonded to the carbonatoms in the medical antimicrobial composition is OH and the number ofammonium nitrogens is N, then N/OH ratio is 0.001 to 0.5.[3] A medical antimicrobial composition, according to [1] or [2]mentioned above, wherein 30% or more of the silicon atoms in the medicalantimicrobial composition are silicon atoms derived from a polarsiloxanyl monomer.[4] A medical antimicrobial composition, according to any one of [1]through [3] mentioned above, wherein at least one component of thesiloxanyl structure-containing polymer (B) has a structure obtained fromthe siloxanyl monomer represented by the following general formula (a)

M-L-Sx  (a)

(where M denotes a radical polymerizable group; L denotes a substitutedor non-substituted divalent organic group with 1 to 20 carbon atoms; andSx denotes a siloxanyl group).[5] A medical antimicrobial composition, according to any one of [1]through [4] mentioned above, wherein the L in the aforementioned formula(a) denotes either of the groups represented by the following generalformulae (b) and (c):

(where j denotes an integer of 1 to 20; k denotes an integer of 1 to 6;and m denotes an integer of 1 to 17; subject to 3k+m≦20).[6] A medical antimicrobial composition, according to [5] mentionedabove, wherein the L in the aforementioned formula (a) denotes a grouprepresented by the general formula (c).[7] A medical antimicrobial composition, according to any one of [4]through [6] mentioned above, wherein at least one component of thesiloxanyl monomer is a polar siloxanyl monomer selected from the groupconsisting of the groups represented by the following formulae (e) and(g):

(in formula (g), Q denotes an alkyl group with 1 to 8 carbon atoms; andp denotes an integer of 1 to 20).[8] A medical antimicrobial composition, according to any one of [1]through [7] mentioned above, wherein the ammonium group-containingpolymer compound (A) has a structure obtained from the ammonium saltmonomer represented by the following general formula (f):

(where R¹ denotes a substituted or non-substituted alkyl group with 1 to30 carbon atoms; R² to R⁷ denote, respectively independently, asubstituent group selected from hydrogen, substituted or non-substitutedalkyl group with 1 to 20 carbon atoms, and substituted ornon-substituted aryl group with 6 to 20 carbon atoms; R² and R³ may alsoform a ring; and X⁻ denotes a given anion).[9] A medical antimicrobial composition, according to any one of [1]through [8] mentioned before, which is obtained by polymerizing themonomers and/or macromonomers constituting the siloxanylstructure-containing polymer (B) in a state of being mixed with thepolymer compound (A).[10] A medical device comprising the medical antimicrobial compositionas set forth in any one of [1] through [9] mentioned above.[11] A medical device, according to [10] mentioned above, which is atleast partially covered with the medical antimicrobial composition asset forth in any one of [1] through [9] mentioned above.[12] A medical device, according to [10] or [11] mentioned above, whichis a molded article containing a silicone resin.[13] A medical device, according to any one of [10] through[12] mentioned above, which has a form selected from a tube and a finerod.[14] A medical device, according to [13] mentioned before, which is oneselected from an endoscope, catheter, infusion tube, gas transfer tube,stent, sheath, cuff, tube connector, access port, drain bag and bloodcircuit.[15] A medical device, according to [13] mentioned above, which is agastrostomy tube.

This invention can provide a medical antimicrobial composition in whichan ammonium group-containing polymer compound is dispersed in asiloxanyl structure-containing polymer. Since said medical antimicrobialcomposition is excellent in transparency, flexibility and mechanicalproperties, the medical device comprising said composition can beenhanced in convenience and quality. Further, since said medicalantimicrobial composition is excellent in adhesion to a base resin withgood mechanical properties, particularly to a silicone resin, the baseresin can be easily coated with said composition, and said medicalantimicrobial composition is unlikely to peel during use. DetailedDescription of the Invention In an embodiment of the medicalantimicrobial composition of this invention, an ammoniumgroup-containing polymer compound (A) is dispersed in a siloxanylstructure-containing polymer (B). In this invention, siloxanyl means astructure containing at least one Si—O—Si bond. In an embodiment of thisinvention, said polymer compound (A) being dispersed in the siloxanylstructure-containing polymer (B) does not include the state where thepolymer compound (A) is merely deposited on the surface of the siloxanylstructure-containing polymer (B), but refers to the state where afterthe medical antimicrobial composition has been ultrasonically washed onthe surface using water, an attempt to extract the polymer compoundcontained in the medical antimicrobial composition using an organicsolvent allows the ammonium group-containing polymer compound (A) to beextracted. In the case where the ammonium group-containing polymercompound (A) can be extracted by said extraction operation, it can bedetermined that said polymer compound (A) is dispersed in said siloxanylstructure-containing polymer (B). Particularly in the case where theammonium group-containing polymer compound (A) can be extracted by 0.1%or more based on the dry weight of the medical antimicrobial compositionby at least one of methanol, ethanol, 2-propanol, toluene, hexane,acetone, methyl ethyl ketone, ethyl acetate, butyl acetate,tetrahydrofuran and dimethyl sulfoxide used as organic solvents, it isdetermined that said polymer compound (A) is dispersed.

Methods for dispersing the polymer compound (A) into the siloxanylstructure-containing polymer (B) for obtaining the medical antimicrobialcomposition in an embodiment of this invention include a methodcomprising the step of producing the siloxanyl structure-containingpolymer (B) by polymerization in the state where the polymer compound ismixed in a raw monomer mixture or raw macromonomer mixture of thesiloxanyl structure-containing polymer (B), and a method comprising thestep of immersing the siloxanyl structure-containing polymer (B) in thesolution of the polymer compound (A) for impregnation, etc. The formermethod is preferred since the content of the polymer compound (A) can beenhanced.

In the case where the siloxanyl structure-containing polymer (B) isproduced by polymerization in the state where the polymer compound (A)is mixed in the monomer mixture, if the content of the polymer compound(A) is too small, sufficient antimicrobial activity cannot be obtained,and if the content is too large, the solid content of the siloxanylstructure-containing polymer (B) becomes small. Therefore, it ispreferred that the content of the polymer compound (A) is 0.1 to 20%. Amore preferred range is 0.5 to 15%, and a further more preferred rangeis 1 to 10%. Each percentage is a percentage by weight expressed withthe total weight (dry weight) of the polymer compound (A) and thesiloxanyl structure-containing polymer (B) as 100.

In the case where the siloxanyl structure-containing polymer (B) isimmersed in the solution of the polymer compound (A) for impregnation,any of various organic and inorganic solvents can be used for thesolution of the polymer compound (A). Examples of the solvent includewater, various alcohol solvents such as methanol, ethanol, propanol,2-propanol, butanol, tert-butanol, tert-amyl alcohol and3,7-dimethyl-3-octanol, various aromatic hydrocarbon solvents such asbenzene, toluene and xylene, various aliphatic hydrocarbon solvents suchas hexane, heptane, octane, decane, petroleum ether, kerosene, ligroinand paraffin, various ketone solvents such as acetone, methyl ethylketone and methyl isobutyl ketone, various ester solvents such as ethylacetate, butyl acetate, methyl benzoate, dioctyl phthalate and ethyleneglycol diacetate, and various glycol ether solvents such as diethylether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether,diethylene glycol dialkyl ether, triethylene glycol dialkyl ether,tetraethylene glycol dialkyl ether, polyethylene glycol dialkyl ether,polyethylene glycol-polypropylene glycol block copolymer andpolyethylene glycol-polypropylene glycol random copolymer. Any one ofthem can be used alone or two or more of them can also be used as amixture. Among them, preferred are alcohol solvents, glycol ethersolvents, water and mixtures consisting of two or more solvents selectedtherefrom. More preferred is water or a water-mixed solvent. Mostpreferred is water.

If the concentration of the solution of the polymer compound (A) is toolow, sufficient antimicrobial activity cannot be obtained, and if theconcentration is too high, it may be necessary to wash the excessiveamount of the polymer compound. Therefore, it is preferred that theconcentration is 0.1 to 30%. A more preferred range is 0.5 to 20%, andthe most preferred range is 1 to 10%. Each percentage is a percentage byweight expressed with the total weight of the solution of the polymercompound (A) as 100.

As the hydrophilic monomer used in the siloxanyl structure-containingpolymer (B) in an embodiment of the medical antimicrobial composition ofthis invention, a monomer having a (meth)acryloyl group, styryl group,allyl group, vinyl group or other polymerizable carbon-carbonunsaturated bond can be suitably used.

Preferred examples of the monomer include carboxylic acids such as(meth)acrylic acid, itaconic acid, crotonic acid and vinylbenzoic acid,(meth)acrylates having a hydroxyl group such as2-hydroxyethyl(meth)acrylate, (meth)acrylamides such asN,N-dimethylacrylamide, N-vinylpyrrolidone, N-vinylimidazole, etc. Amongthem, in view the mechanical properties and long-term storage stabilityof the obtained siloxanyl structure-containing polymer (B),(meth)acrylamides such as N,N-dimethylacrylamide are preferred.

If the content of the siloxanyl component in the medical antimicrobialcomposition is too small, the medical antimicrobial composition used asa coating material is poor in adhesion to a silicone resin, etc., and ifthe content is too large, transparency is impaired. Therefore, it ispreferred that the silicon atom content is 2 to 30 wt %, with the dryweight of the medical antimicrobial composition as 100 wt %. A morepreferred range is 3 to 28 wt %, and the most preferred range is 5 to 25wt %. The silicon atom content of the medical antimicrobial compositioncan be obtained by inductively coupled plasma atomic emissionspectroscopy.

To obtain sufficient compatibility between the hydrophobic siloxanylcomponent of the siloxanyl structure-containing polymer (B) and thehydrophilic ammonium group-containing polymer compound (A), it ispreferred that the silicon atoms derived from a polar siloxanyl monomeraccount for 30% or more of the silicon atoms in the siloxanyl component.More preferred is 40% or more, and most preferred is 50% or more.

In the above, the polar siloxanyl monomer refers to a siloxanyl monomerhaving a polar group in the molecule. Examples of the polar groupinclude a hydroxyl group, amide group, carboxyl group, amino group,carbonate group, carbamate group, sulfoneamide group, sulfonic acidgroup, phosphonic acid group, alkoxy group with 1 to 3 carbon atoms,etc. In view of the effects of achieving the compatibility between thesiloxanyl structure-containing polymer (B) and the polymer compound (A)and transparency, a hydroxyl group is most preferred.

Further, for enhancing transparency, it is preferred that the medicalantimicrobial composition in an embodiment of this invention iscopolymerized with a hydrophilic monomer, particularly a (meth)acrylatemonomer having a hydroxyl group such as 2-hydroxyethyl(meth)acrylate. Ifthe amount of the monomer used is too small, the effect of enhancingtransparency is unlikely to be obtained, and if the amount is too large,the physical properties of the polymer are affected. Therefore, it ispreferred that the amount of the monomer is 0.1 to 25 parts by weightper 100 parts by weight as the dry weight of the siloxanylstructure-containing polymer (B). A more preferred range is 0.5 to 20parts by weight, and the most preferred range is 1.0 to 15 parts byweight.

Furthermore, if the N/OH ratio (where OH denotes the number of hydroxylgroups bonded to the carbon atoms in the medical antimicrobialcomposition, and N denotes the number of ammonium nitrogens) is toosmall, sufficient antimicrobial activity cannot be obtained, and if theratio is too large, the obtained medical antimicrobial composition isnot transparent enough. Therefore, it is preferred that the ratio is0.001 to 0.5. A more preferred range is 0.005 to 0.4, and the mostpreferred range is 0.01 to 0.3. Moreover, the method for measuring theN/OH ratio is selected in response to the components of the siloxanylstructure-containing polymer (B) and the polymer compound (A) and thecontents thereof. For example, general various measurement methods suchas nuclear magnetic resonance (NMR), infrared spectroscopy (IR),elementary analysis, attenuated total reflection infrared absorptionspectroscopy (ATR), ultraviolet spectroscopy (UV) and titration, andcombinations thereof can be enumerated.

Polymerization methods for producing the siloxanyl structure-containingpolymer (B) used in the medical antimicrobial composition in anembodiment of this invention include a method comprising the step ofpolymerizing a mixture consisting of various monomers such as asiloxanyl monomer, hydrophilic monomer and crosslinking monomer, amethod comprising the steps of homopolymerizing or copolymerizingvarious monomers such as a siloxanyl monomer and hydrophilic monomer andsubsequently polymerizing the macromonomers having polymerizable groupsintroduced therein, etc.

In the case where the siloxanyl structure-containing polymer (B) of themedical antimicrobial composition in an embodiment of this invention canbe produced by polymerizing monomers, it is preferred that the siloxanylmonomer is a siloxanyl monomer with a structure having one polymerizablegroup in the molecule, represented by the following general formula (a):

M-L-Sx  (a)

In the formula (a), M denotes a radical polymerizable group. Examples ofthe radical polymerizable group include a vinyl group, allyl group,vinyloxy group, allyloxy group, vinyl carbamate group, allyl carbamategroup, vinyl carbonate group, allyl carbonate group, methacryloyl group,acryloyl group, styryl group, etc. Among them, an acryloyl group andmethacryloyl group are preferred in view of the elastic modulus of theobtained polymer.

In the formula (a), L denotes a substituted or non-substituted divalentorganic group with 1 to 20 carbon atoms. In order to lower the elasticmodulus of the obtained polymer, an alkylene group is more preferred,and in order to achieve the compatibility with the hydrophilic monomer,an organic group having a hydroxyl group or an ethylene oxide structureis more preferred. Examples of the organic group include divalenthydrocarbon groups such as methylene group, ethylene group, propylenegroup, methylethylene group, propylene group, butylene group,methylpropylene group, dimethylpropylene group and pentylene group,divalent organic groups having a hydroxyl group such as hydroxypropylenegroup and hydroxybutylene group, divalent organic groups having an etherbond represented by the following formulae (L-1) to (L-3), etc.,divalent organic groups having an ether bond and a hydroxyl grouptogether represented by the following formulae (L-4) and (L-5), etc.

Among them, the group represented by the following formula (b) or (c)

is preferred, and the group represented by formula (c) is morepreferred. Further, the group represented by formula (c) where k denotes1 and m denotes 1 to 5 is preferred, and the group represented byformula (c) where k denotes 1 and m denotes 3 is most preferred.

In the formula (a), Sx denotes a siloxanyl group. In this case, thesiloxanyl group refers to a group having at least one Si—O—Si bond inthe structure thereof.

It is preferred that the siloxanyl monomer represented by theabovementioned general formula (a) is represented by the followinggeneral formula (a′).

where n denotes an integer of 0 to 200; a, b and c denote, respectivelyindependently, an integer of 0 to 20. The number of n+a+b+c decides thenumber of siloxane bonds in the siloxanyl compound. If the number ofn+a+b+c is too small, the medical antimicrobial composition applied as acoating material is not sufficient in adhesion to a silicone resin,etc., and if the number is too large, the transparency is impaired.Therefore, it is preferred that the number is 1 to 260. A more preferredrange is 2 to 100, and a further more preferred range is 2 to 50. Themost preferred range is 2 to 15.

In the formula (a′), A¹ to A¹¹ denote, respectively independently, asubstituted or non-substituted alkyl group with 1 to 20 carbon atoms orsubstituted or non-substituted aryl group with 6 to 20 carbon atoms. Inthe structure of the abovementioned formula (a′), among the substituentgroups represented by the following formula (j)

the especially suitable group can be selected from the group consistingof tris(trimethylsiloxy)silyl group, methyl-bis(trimethylsiloxy)silylgroup, dimethyl(trimethylsiloxy)silyl group and poly(dimethylsiloxane)group for such reasons that a compound having such a substituent groupis industrially available relatively at a low price and that a medicalantimicrobial composition with high oxygen permeability and hightransparency can be obtained. In this case, the poly(dimethylsiloxane)group is a substituent group represented by formula (j), where a=b=c=0;n denotes an integer of 2 to 15; each of A¹, A², A⁹ and A¹¹ denotes amethyl group; and A¹⁰ denotes an alkyl group with 1 to 10 carbon atoms,preferably a methyl group or butyl group, most preferably a butyl group.

Among the siloxanyl monomers represented by the general formula (a), thesiloxanyl monomers represented by the following formulae (d), (e) and(g)

(in formula (g), Q denotes an alkyl group with 1 to 8 carbon atoms; andp denotes an integer of 1 to 20) are preferred in view of thecompatibility with the hydrophilic monomer and ammonium salt monomer,and the oxygen permeability and mechanical properties of the polymerobtained by polymerization. Further, a siloxanyl monomer having ahydroxyl group in the molecule as represented by formula (e) or (g) ismost preferred for the reason that even if the siloxanyl monomer ismixed with an internal wetting agent such as polyvinylpyrrolidone, atransparent siloxanyl structure-containing polymer can be easilyobtained.

In this description, a macromonomer refers to a monomer with a molecularweight (formular weight) of 800 or more having one or more polymerizablegroups. In the case where the siloxanyl structure-containing polymer (B)used in the medical antimicrobial composition in an embodiment of thisinvention is obtained from macromonomers, a method comprising the stepsof homopolymerizing any of the abovementioned various siloxanylmonomers, subsequently introducing polymerizable groups thencopolymerizing it with any of various hydrophilic monomers, etc., or amethod comprising the steps of copolymerizing any of various siloxanylmonomers, any of various hydrophilic monomers, etc. and subsequentlyintroducing polymerizable groups then polymerizing it can be used. Amongthese methods, a method of copolymerizing any of various siloxanylmonomers and any of various hydrophilic monomers and subsequentlyintroducing polymerizable groups then polymerizing it is preferred sincethe compatibility between the siloxanyl component and the hydrophiliccomponent tend to be high.

If the weight average molecular weight of the siloxanyl macromonomer istoo low, the effect of inhibiting polymerization shrinkage as one of theadvantages of using a macromonomer is insufficient, and if it is toohigh, such problems that the viscosity of the macromonomer becomes sohigh as to inconvenience handling and that the solubility in thepolymerization solvent declines arise. Therefore, it is preferred thatthe weight average molecular weight is 1,000 to one million. A morepreferred range is 3,000 to 500,000, and the most preferred range is5,000 to 100,000. The weight average molecular weight is obtained byanalyzing under the following conditions using size exclusionchromatography.

-   -   Columns: TSKgel Super HM-H two columns in series    -   Mobile phase: N-methylpyrrolidone (containing 10 mM of LiBr)    -   Column temperature: 40° C.    -   Flow rate of mobile phase: 0.2 mL/min    -   Measuring time: 40 minutes    -   Sample concentration: 0.4 wt % (N-methylpyrrolidone solvent)    -   Injected amount: 10 μl    -   In terms of standard polystyrene    -   Detector: RI detector

The polymer compound (A) used in the medical antimicrobial compositionin an embodiment of this invention is not a crosslinked polymer compoundbut a polymer compound that can be dissolved in a solvent.

The ammonium salt monomer constituting the polymer compound (A) used inthe medical antimicrobial composition in an embodiment of this inventionis a monomer having a polymerizable group and an ammonium group(ammonium cation) in the molecule. As the polymerizable group, a radicalpolymerizable group is preferred, and can be a (meth)acryloyl group,(meth)acrylamide group, styryl group, allyl group, vinyl group or otherradical polymerizable group having a carbon-carbon unsaturated bond.Further, one of preferred modes of the ammonium group (ammonium cation)is an alkyl group with 1 to 20 carbon atoms having one substituent groupconnected with a polymerizable group, on the nitrogen atom of theammonium group, in which the other three substituent groups may berespectively independently substituted, or a substituted ornon-substituted aryl group with 6 to 20 carbon atoms. Suitable examplesof the aforementioned substituent group connected with a polymerizablegroup include a (meth)acryloyloxyethyl group, (meth)acryloyloxypropylgroup, (meth)acryloylaminoethyl group, (meth)acryloylaminopropyl group,(meth)acryloyloxyethyl aminocarbonyloxy ethyl group,(meth)acryloyloxyethyl aminocarbonyloxy propyl group, styryl group,styrylethyl group, styrylmethyl group, etc. Further, another preferredmode of an ammonium group is a case where the nitrogen atom of theammonium group constitutes a nitrogen-containing hetero ring. Preferredexamples of the nitrogen-containing hetero ring include an imidazolering, imidazolidine ring, pyrazole ring, pyrazolidine ring, pyrrolering, pyrrolidine ring, oxazole ring, oxazolidine ring, isoxazole ring,isoxasolidine ring, piperidine ring, pyridine ring, pyrazine ring,piperazine ring, pyrimidine ring, pyridazine ring, morpholine ring,quinoline ring, indoline ring, etc. Among them, an ammonium salt monomerhaving an imidazole ring is especially preferred in view of thetransparency of the medical antimicrobial composition. More particularexamples of the structure are the ammonium salt monomers represented bythe following general formulae (f), (h) and (i)

(in formula (f), R¹ denotes a substituted or non-substituted alkyl groupwith 1 to 30 carbon atoms; R² to R⁷ denote, respectively independently,a substituent group selected from hydrogen, substituted ornon-substituted alkyl group with 1 to 20 carbon atoms, and substitutedor non-substituted aryl group with 6 to 20 carbon atoms; R² and R³ mayalso form a ring; and X⁻ denotes a given anion.)

(in formulae (h) and (i), R⁸ to R¹⁰ denote, respectively independently,a substituted or non-substituted alkyl group with 1 to 20 carbon atomsor substituted or non-substituted aryl group with 6 to 20 carbon atoms;R¹¹ denotes hydrogen or methyl group; Z denotes O or NH; and X⁻ denotesa given anion). Among them, a vinyl imidazolium salt represented by thegeneral formula (f) is most preferred in view of the transparency,thermal stability and antimicrobial activity of the medicalantimicrobial composition.

In the general formula (f), R¹ denotes a substituted or non-substitutedalkyl group with 1 to 30 carbon atoms. If the number of carbon atoms issmall, the compatibility with the siloxanyl monomer declines due to thehydrophilicity of the ammonium cation portion, and if the number ofcarbon atoms is too large, the compatibility with the hydrophilicmonomer declines. Therefore, it is more preferred that the number ofcarbon atoms is 4 to 20. Suitable examples of the group are alkyl groupssuch as butyl group, hexyl group, octyl group, decyl group, undecylgroup, dodecyl group, tetradecyl group, hexadecyl group and octadecylgroup.

In the general formula (f), R² to R⁷ denote, respectively independently,a substituted group selected from hydrogen, substituted ornon-substituted alkyl groups with 1 to 20 carbon atoms and substitutedand non-substituted aryl groups with 6 to 20 carbon atoms. Suitableexamples of R² to R⁷ include alkyl groups such as methyl group, ethylgroup, propyl group, butyl group, hexyl group, octyl group, decyl group,undecyl group, dodecyl group, tetradecyl group, hexadecyl group andoctadecyl group; substituted alkyl groups such as benzyl group; and arylgroups such as phenyl group. A more preferred example is hydrogen ormethyl group, and the most preferred example is hydrogen. Further, inanother mode, R² and R³ may also form a ring. That is, R² and R³ may becombined with each other to form a ring condensed to an imidazole ring.In this case, a suitable example of the condensed ring formed of R², R³and imidazole ring is a benzimidazole ring.

In the general formulae (h) and (i), R⁸ to R¹⁰ denote, respectivelyindependently, a substituted or non-substituted alkyl group with 1 to 20carbon atoms or substituted or non-substituted aryl group with 6 to 20carbon atoms. Suitable examples of R⁸ to R¹⁰ include alkyl groups suchas methyl group, ethyl group, propyl group, butyl group, hexyl group,octyl group, decyl group, undecyl group, dodecyl group, tetradecylgroup, hexadecyl group and octadecyl group; substituted alkyl groupssuch as benzyl group; and aryl groups such as phenyl group.

In the general formulae (f), (h) and (i), X⁻ denotes a given anion.Examples of the anion include halide ions such as fluoride ion, chlorideion, bromide ion and iodide ion, hydroxide ion, sulfate ion, nitrate ionand tetrafluoroboron ion, etc. Among them, in view of easy synthesis, ahalide ion is preferred, and in view of solubility, a bromide ion oriodide ion is most preferred.

The polymer compound (A) in one aspect of this invention can be thehomopolymer of an ammonium salt monomer or a copolymer with anothermonomer. If the total weight of the respective monomers in the copolymeris 100 parts by weight, it is preferred that the ammonium salt monomercontent is 1 part by weight or more, since otherwise sufficientantimicrobial activity cannot be obtained. More preferred are 10 partsby weight or more, and most preferred are 30 parts by weight or more.

In the case where another monomer than the ammonium salt monomer iscopolymerized to obtain the polymer compound (A) used in the medicalantimicrobial composition in an embodiment of this invention, a monomerhaving a (meth)acryloyl group, styryl group, allyl group, vinyl group orother polymerizable carbon-carbon unsaturated bond can be used as theother monomer. Examples of the monomer include amide monomers such asN-vinylpyrrolidone, N,N-dimethylacrylamide, N-vinylformamide andN-vinylacetamide, monomers having a hydroxyl group such as2-hydroxyethyl methacrylate, N-(2-hydroxyethyl)acrylamide and2-(2-hydroxyethoxy)ethyl methacrylate, siloxanyl monomers such as3-tris(trimethylsiloxy)silylpropyl methacrylate and polydimethylsiloxanewith(meth)acryl group(s) at one end or both ends. Among them, amidemonomers and monomers having a hydroxyl group are preferred since thecompatibility with the ammonium salt monomer can be easily obtained.Among them, N-vinylpyrrolidone, N,N-dimethylacrylamide, 2-hydroxyethylmethacrylate and N-(2-hydroxyethyl) acrylamide are preferred.N-vinylpyrrolidone is most preferred.

If the weight average molecular weight of the polymer compound (A) usedin the medical antimicrobial composition is too low, the polymercompound (A) is likely to be dissolved out from the medicalantimicrobial composition, and if it is too high, the solubility of thepolymer compound (A) in the monomer mixture and in the impregnationsolution declines. Therefore, it is preferred that the weight averagemolecular weight is 1,000 to one million. A more preferred range is5,000 to 500,000, and the most preferred range is 10,000 to 300,000.

If the content of the polymer compound (A) used in the medicalantimicrobial composition is too small, sufficient antimicrobialactivity cannot be obtained, and if it is too large, sufficienttransparency cannot be obtained. Therefore, it is preferred that thecontent is 0.01 to 20 wt %. A more preferred range is 0.5 to 15 wt %,and the most preferred range is 1 to 10 wt %. Each percentage is apercentage by weight expressed with the dry weight of the medicalantimicrobial composition as 100.

For the medical antimicrobial composition in an embodiment of thisinvention, a monomer having two or more copolymerizable carbon-carbonunsaturated bonds in each molecule can be used as a comonomer for suchreasons that good mechanical properties can be obtained and that goodresistance to disinfectants and cleaning fluids can be obtained. In thiscase, it is preferred that the copolymerization rate of the monomerhaving two or more copolymerizable carbon-carbon unsaturated bonds ineach molecule is 0.1 to 20 wt % with the dry weight of the medicalantimicrobial composition as 100 wt %. A more preferred range is 0.3 to10 wt %, and a further more preferred range is 0.5 to 5 wt %.

The medical antimicrobial composition in an embodiment of this inventionmay contain an ultraviolet light absorber, coloring matter or colorant,etc. Further, the composition may also have an ultraviolet lightabsorber and dye or colorant, each having a polymerizable group,copolymerized therewith.

In the case where the medical antimicrobial composition in an embodimentof this invention is produced by polymerization, it is preferred to adda thermal polymerization initiator or photo polymerization initiatortypified by a peroxide or azo compound. In the case where thermalpolymerization is performed, an initiator with an optimum polymerizationproperty at a desired reaction temperature should be selectively used.In general, an azo initiator or peroxide initiator with a 10-hourhalf-life temperature of 40° C. to 120° C. is suitable. Examples of thephoto polymerization initiator include carbonyl compounds, peroxides,azo compounds, sulfur compounds, halogen compounds, metal salts, etc.Any one of these polymerization initiators can be used alone or two ormore of them can also be used as a mixture. The amount of the initiatoris about up to 1 wt %.

In the case where the medical antimicrobial composition in an embodimentof this invention is produced by polymerization, a polymerizationsolvent can be used. As the solvent, any of various organic andinorganic solvents can be used. Examples of the solvent include water,various alcohol solvents such as methanol, ethanol, propanol,2-propanol, butanol, tert-butanol, tert-amyl alcohol and3,7-dimethyl-3-octanol, various aromatic hydrocarbon solvents such asbenzene, toluene and xylene, various aliphatic hydrocarbon solvents suchas hexane, heptane, octane, decane, petroleum ether, kerosene, ligroinand paraffin, various ketone solvents such as acetone, methyl ethylketone and methyl isobutyl ketone, various ester solvents such as ethylacetate, butyl acetate, methyl benzoate, dioctyl phthalate and ethyleneglycol diacetate, and various glycol ether solvents such as diethylether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether,diethylene glycol dialkyl ether, triethylene glycol dialkyl ether,tetraethylene glycol dialkyl ether, polyethylene glycol dialkyl ether,polyethylene glycol-polypropylene glycol block copolymer andpolyethylene glycol-polypropylene glycol random copolymer. Any one ofthem can be used alone or two or more of them can also be used as amixture.

The medical device in an embodiment of this invention comprises theaforementioned medical antimicrobial composition. One of preferred modesof the medical device in an embodiment of this invention is a moldedarticle at least partially formed of the aforementioned medicalantimicrobial composition. Another one of preferred modes of the medicaldevice in an embodiment of this invention is a molded article at leastpartially formed of a base resin and at least partially covered with theaforementioned medical antimicrobial composition.

As the base resin, a resin generally used as medical devices ispreferred. Examples of the resin include olefin resins such aspolyethylene, polypropylene and cyclic polyolefin resins, vinyl resinssuch as polyvinyl chloride, polyvinyl acetate and polyvinyl alcohol,urethane resins, acrylic resins, epoxy resins, polyester resins,polyamide resins, phenoxy resins, natural rubbers, silicone resinstypified by polydimethylsiloxane, and synthetic rubbers. Further,copolymers comprising the monomers constituting these polymers, mixturesof these polymers, and various copolymers and mixtures obtained bymixing a plasticizer, reinforcing agent, stabilizer, polymerizationinitiator, polymerization accelerator or contrast medium, etc. withthese polymers can also be used. In the case of a copolymer, variouscopolymerization modes can be employed, and any of randomcopolymerization, block copolymerization and graft copolymerization canalso be used. As the aforementioned base resin, a silicone resin is mostpreferred in view of chemical stability, heat resistance, etc.

The medical device in an embodiment of this invention can suitably atleast partially have a form selected from a tube and a fine rod.Suitable examples of the medical device include an endoscope, catheter,infusion tube (including a gastrostomy tube), gas transfer tube, stent,sheath, cuff, tube connector, access port, drain bag and blood circuit.

In the case where the medical device in an embodiment of this inventionis at least formed of a base resin and at least partially covered withthe aforementioned medical antimicrobial composition, the polymerizationmethods and molding methods suitably used for obtaining the medicaldevice formed of a base resin include injection molding, extrusion,cutting work, mold polymerization, etc. In this case, the medical devicein an embodiment of this invention is at least partially covered withthe aforementioned medical antimicrobial composition. Examples of thecovering method in this case are described below.

A mixture consisting of the ammonium group-containing polymer compound(A) and the siloxanyl structure-containing polymer (B) is hereinafterreferred to as CX.

A mixture consisting of the ammonium group-containing polymer compound(A) and the monomer composition destined to constitute the siloxanylstructure-containing polymer (B) by polymerization is hereinafterreferred as CY.

Examples of the covering method include a method comprising the steps ofimmersing the molded article of the aforementioned base resin in a CXsolution and subsequently taking it out of the solution, for drying, amethod comprising the steps of spraying a CX solution to theaforementioned molded article and subsequently drying, a methodcomprising the steps of directly coating the aforementioned moldedarticle with a CX solution using an absorbing body such as a brush,cloth or sponge impregnated with the CX solution and subsequentlydrying, a method comprising the steps of immersing the aforementionedmolded article in the CY or a solution thereof, subsequently taking out,as required drying the solvent, and polymerizing, a method comprisingthe steps of spraying the CY or a solution thereof to the aforementionedmolded article, subsequently as required drying the solvent, andpolymerizing, a method comprising the steps of directly coating theaforementioned molded article with the CY or a solution thereof using anabsorbing body such as a brush, cloth or sponge impregnated with the CYor the solution thereof, subsequently as required drying the solvent,and polymerizing, etc.

If the thickness of the applied medical antimicrobial composition is toothin, it is difficult to obtain sufficient antimicrobial activity, andif it is too thick, it tends to be difficult to insert the medicaldevice into a fine body cavity. Therefore, it is preferred that thethickness is 0.1 μm to 5 mm. A more preferred range is 1 μm to 100 μm,and an especially preferred range is 5 μm to 50 μm.

Further, in the case where good adhesion is unlikely to be obtained whenthe molded article is covered with the medical antimicrobialcomposition, it is preferred that the molded article is treated to bereformed before it is coated with the medical antimicrobial composition.The reforming treatment method can be irradiation with electromagneticwaves (including light), irradiation with a corpuscular beam such aselectron beam, plasma treatment, chemical vapor deposition treatmentsuch as vacuum evaporation or sputtering, heating, base treatment, acidtreatment, use of any other appropriate surface treating agent, andcombinations thereof.

Among these reforming means, ultraviolet light irradiation, plasmatreatment, base treatment and acid treatment are preferred since theyare simple.

In ultraviolet light irradiation, a high pressure mercury lamp, lowpressure mercury lamp or excimer light irradiation can be preferablyused.

In plasma treatment, a chemically highly active layer can be formed,though the activity is either oxidative or reducing, depending on thegas used. Suitable examples of the gas used include inert gases such asnitrogen, carbon dioxide, argon, helium, neon and argon,fluorine-containing gases such as carbon tetrafluoride andchlorofluorocarbon, oxygen, hydrogen, air and mixed gases thereof.

As the device for applying the aforementioned plasma treatment, it ispreferred to use a vacuum chamber equipped with a high-frequency,low-frequency or other transmitter, and a so-called atmospheric pressureplasma device can also be suitably used. In the atmospheric pressureplasma device, since a plasma gas state of atmospheric pressure can beformed, a surface layer can be activated simply without requiring apressure reducing device or vessel. The treatment by a high frequency isvery effective, and usually a device of 13.56 MHz can be preferablyused. Further, the output can be appropriately selected in reference tothe size of the device and the molded article to be treated, but isusually 10 to 500 W. The treatment time is selected likewise, butusually a period of about 10 to 20 minutes can provide a sufficienteffect.

The base treatment or acid treatment can be performed, for example, by amethod of bringing the molded article into contact with a basic oracidic solution or a method of bringing the molded article into contactwith a basic or acidic gas, etc. More particular methods include, forexample, a method of immersing the molded article into a basic or acidicsolution, a method of spraying a basic or acidic solution or a basic oracidic gas to the molded article, a method of coating the molded articlewith a basic or acidic solution using a knife or brush, etc., a methodof spin-coating or dip-coating the molded article with a basic or acidicsolution, etc. The simplest method for obtaining a large reformingeffect is to immerse the molded article into a basic or acidic solution.

Further, in the case where good adhesion is unlikely to be obtained whenthe molded article is covered with the medical antimicrobialcomposition, a method of coating the molded article with a primerbeforehand can be preferably used. The primer used should beappropriately selected in response to the base resin used, but asolution with a bifunctional compound such as diphenylmethanediisocyanate, toluene diisocyanate or hexamethylene diisocyanate or asilane coupling compound such as RTV (room temperature vulcanizing)silicone dissolved in an organic solvent is a suitable example.

If the viscosity of a CX solution, CY or a solution thereof is too high,it is difficult to cover uniformly, and if it is too low, severalcovering operations may be necessary to obtain a covering layer with asuitable thickness, to lower working efficiency. Therefore, it ispreferred that the viscosity of the solution with the mixture dissolvedat a concentration of 3 to 20 wt %, preferably 5 to 10 wt % is 0.01 P to100 P. A more preferred range is 0.05 P to 60 P, and an especiallypreferred range is 0.1 P to 40 P.

In the case where the medical device is at least partially formed of themedical antimicrobial composition, suitable polymerization methods andmolding methods for producing the medical device of this inventioninclude injection molding, extrusion, cutting work, mold polymerization,etc.

As an example, a case where the medical antimicrobial composition ofthis invention is molded by a mold polymerization method is explainedbelow.

A mixture (CY) consisting of an ammonium group-containing polymercompound (A) and a monomer composition constituting a siloxanylstructure-containing polymer (B) is made to fill the cavity of a moldwith a certain shape. Then, photo polymerization or thermalpolymerization is performed to form the mixture in the shape of themold. The mold is formed of a resin, glass, ceramic or metal, etc., butin the case of photo polymerization, an optically transparent materialis used, and usually a resin or glass is used. When a molded article isproduced, in most cases, a cavity is formed by two mold members facingeach other, and is filled with the CY. However, depending on the shapeof the mold and the properties of the CY, a gasket intended to let themolded article have a certain thickness and to prevent the leak of thefilling CY may also be used together. In succession, the mold having thecavity filled with the CY is irradiated with active light such asultraviolet light or heated in an oven or liquid tank, to polymerize theCY. A method of using both photo polymerization and heat polymerizationby performing heat polymerization after photo polymerization or on thecontrary performing photo polymerization after heat polymerization canalso be employed. In the case of photo polymerization, irradiating themolded article with light containing much ultraviolet light for a shortperiod of time (usually 1 hour or less), for example, with a mercurylamp or insect collection lamp as the light source is general. In thecase of thermal polymerization, a condition of gradually heating fromabout room temperature to reach a temperature of 60° C. to 200° C.,taking several hours to tens of hours is preferred for holding theoptical uniformity and quality of the molded article and for enhancingthe reproducibility.

The medical antimicrobial composition in an embodiment of this inventioncan be treated to be reformed by various methods. It is preferred toperform the reforming treatment of enhancing the water wettability ofthe surface.

Particular reforming methods include irradiation with electromagneticwaves (including light), irradiation with a corpuscular beam such aselectron beam, plasma treatment, chemical vapor deposition treatmentsuch as vacuum evaporation or sputtering, heating, base treatment, acidtreatment, use of any other appropriate surface treating agent, andcombinations thereof. Among these reforming means, base treatment andacid treatment are preferred since they are simple.

Examples of the base treatment or acid treatment include a method ofbringing the medical antimicrobial composition into contact with a basicor acidic solution, a method of bringing the medical antimicrobialcomposition into contact with a basic or acidic gas, etc. Moreparticular methods include, for example, a method of immersing themedical antimicrobial composition in a basic or acidic solution, amethod of spraying a basic or acidic solution or a basic or acidic gasto the medical antimicrobial composition, a method of coating themedical antimicrobial composition with a basic or acid solution using aknife, brush, etc., a method of spin-coating or dip-coating the medicalantimicrobial composition with a basic or acidic solution, etc. Thesimplest method for obtaining a large reforming effect is a method ofimmersing the medical antimicrobial composition in a basic or acidicsolution.

The temperature at which the medical antimicrobial composition isimmersed in a basic or acidic solution is not especially limited, but isusually in a range from about −50° C. to about 300° C. Consideringworking efficiency, a temperature range from −10° C. to 150° C. is morepreferred, and the most preferred range is −5° C. to 60° C.

The optimum period of time during which the medical antimicrobialcomposition is immersed in a basic or acidic solution depends on thetemperature, but generally a period of 0.1 to 100 hours is preferred. Aperiod of 0.3 to 24 hours is more preferred, and a period of 0.5 to 12hours is most preferred. If the contact period of time is too short, asufficient treatment effect cannot be obtained, and if the contactperiod of time is too long, working efficiency and productivity declinewhile such adverse effects as lower oxygen permeability and lowermechanical properties may occur as the case may be.

Examples of the base include alkali metal hydroxides, alkaline earthmetal hydroxides, various carbonates, various borates, variousphosphates, ammonia, various ammonium salts, various amines, highmolecular weight bases such as polyethyleneimine and polyvinylamine,etc. Among them, an alkali metal hydroxide is most preferred in view oflow price and large treatment effect.

Examples of the acid include various inorganic acids such as sulfuricacid, phosphoric acid, hydrochloric acid and nitric acid, variousorganic acids such as acetic acid, formic acid, benzoic acid and phenol,various high molecular weight acids such as polyacrylic acid andpolystyrenesulfonic acid. Among them, high molecular weight acids arepreferred in view of high treatment effect and less adverse effects onother physical properties, and among them, polyacrylic acid is mostpreferred in view of acidity and solubility.

As the solvent of the basic or acidic solution, any of various inorganicand organic solvents can be used. Examples of the solvent include water,various alcohols such as methanol, ethanol, propanol, 2-propanol,butanol, ethylene glycol, diethylene glycol, triethylene glycol,tetraethylene glycol, polyethylene glycol and glycerol, various aromatichydrocarbons such as benzene, toluene and xylene, various aliphatichydrocarbons such as hexane, heptane, octane, decane, petroleum ether,kerosene, ligroin and paraffin, various ketones such as acetone, methylethyl ketone and methyl isobutyl ketone, various esters such as ethylacetate, butyl acetate, methyl benzoate and dioctyl phthalate, variousethers such as diethyl ether, tetrahydrofuran, dioxane, ethylene glycoldialkyl ether, diethylene glycol dialkyl ether, triethylene glycoldialkyl ether, tetraethylene glycol dialkyl ether and polyethyleneglycol dialkyl ether, various aprotic polar solvents such asdimethylformamide, dimethylacetamide, N-methyl-2-pyrrolidone,dimethylimidazolidinone, hexamethyl phosphoric triamide and dimethylsulfoxide, halogen containing solvents such as methylene chloride,chloroform, dichloroethane, trichloroethane and trichloroethylene, andchlorofluorocarbon solvents, etc. Among them, water is most preferred inview of economy, simple handling, chemical stability, etc. As thesolvent, a mixture consisting of two or more solvents can also be used.The basic or acidic solution used may also contain ingredients otherthan the basic or acidic substance and the solvent.

After completion of base treatment or acid treatment, the medicalantimicrobial composition can be washed to remove the basic or acidicsubstance. As the washing solvent, any of various inorganic and organicsolvents can be used. Examples of the solvent include water, variousalcohols such as methanol, ethanol, propanol, 2-propanol, butanol,ethylene glycol, diethylene glycol, triethylene glycol, tetraethyleneglycol, polyethylene glycol and glycerol, various aromatic hydrocarbonssuch as benzene, toluene and xylene, various aliphatic hydrocarbons suchas hexane, heptane, octane, decane, petroleum ether, kerosene, ligroinand paraffin, various ketones such as acetone, methyl ethyl ketone andmethyl isobutyl ketone, various esters such as ethyl acetate, butylacetate, methyl benzoate and dioctyl phthalate, various ethers such asdiethyl ether, tetrahydrofuran, dioxane, ethylene glycol dialkyl ether,diethylene glycol dialkyl ether, triethylene glycol dialkyl ether,tetraethylene glycol dialkyl ether and polyethylene glycol dialkylether, various aprotic polar solvents such as dimethylformamide,dimethylacetamide, N-methyl-2-pyrrolidone, dimethylimidazolidinone,hexamethyl phosphoric triamide and dimethyl sulfoxide, halogencontaining solvents such as methylene chloride, chloroform,dichloroethane, trichloroethane and trichloroethylene, andchlorofluorocarbon solvents, etc.

As the washing solvent, a mixture consisting of two or more solvents canalso be used. The washing solvent may also contain ingredients otherthan the solvent, for example, an inorganic salt, surfactant andcleaning agent.

The reforming treatment may also be applied to the medical antimicrobialcomposition as a whole or only to a portion such as the surface of themedical antimicrobial composition. If the reforming treatment is appliedto the surface only, the water wettability of the surface only can beenhanced without greatly changing the nature of the medicalantimicrobial composition as a whole.

Another method for enhancing the water wettability of the surface of themedical antimicrobial composition in an embodiment of this invention isan internal wetting agent method in which a monomer mixture to bepolymerized is polymerized in the state where the monomer mixturecontains a hydrophilic polymer to ensure that the medical antimicrobialcomposition may hold the hydrophilic polymer, to enhance the waterwettability of the surface thereof. Examples of the hydrophilic polymerused as the internal wetting agent include polyvinyl cyclic amides suchas polyvinylpyrrolidone, polyvinyl cyclic amines such aspolyvinylimidazole, polyacrylamides such as poly-N,N-dimethylacrylamide,polyalcohols such as polyvinyl alcohol, polycarboxylic acids such aspolyacrylic acid, polyethylene glycols, mixtures and copolymers thereof,etc. Among them, polyvinylpyrrolidone is most preferred in view of thewater wettability enhancement of the surface of the medicalantimicrobial composition.

It is not preferred that the oxygen permeability of the medicalantimicrobial composition in an embodiment of this invention is too lowfor the reason that in the case where the medical antimicrobialcomposition is applied especially to an artificial lung or artificialheart-lung, etc., oxygen gas permeation is inhibited. It is notpreferred either that the oxygen permeability is too high since theadhesion to a silicone resin declines. It is preferred that the oxygenpermeability coefficient is 1×10⁻¹¹ to 800×10⁻¹¹ (cm²/sec)mLO₂/(mL·hPa).More preferred is 10×10⁻¹¹ to 500×10⁻¹¹ (cm²/sec)mLO₂/(mL·hPa).

With regard to the antimicrobial activity of the medical antimicrobialcomposition of this invention, in the case where the plate counts ofthree samples are measured using Pseudomonas aeruginosa, if the meanvalue of the three plate counts after completion of culture is within 4times the mean value of the three initial plate counts before culture,it is determined that no proliferation occurred, and that theantimicrobial composition has an antimicrobial effect. It is morepreferred that the mean value after completion of culture is 10% or lessof the mean value of plate counts of controls and it is most preferredthat the mean value after completion of culture is 1% or less of themean value of plate counts of controls.

EXAMPLES

Embodiments of this invention are explained below particularly inreference to examples. Meanwhile, 2-propanol may be referred to as IPAas the case may be.

Working Example 1

Twenty eight point eight parts by weight of the siloxanyl compoundrepresented by the following formula (y1)

35.5 parts by weight of N,N-dimethylacrylamide, 26.8 parts by weight ofthe polydimethylsiloxane methacrylated at one end represented by thefollowing formula (y2)

(“Silaplane” FM-0711 produced by Chisso Corporation, weight averagemolecular weight about 1,000), 3.8 parts by weight of 2-hydroxyethylmethacrylate, 3.0 parts by weight of tri(ethylene glycol)dimethacrylate,5 parts by weight of an ammonium group-containing polymer compound(weight average molecular weight about 40,000, a copolymer ofN-vinylpyrrolidone/vinylmethylimidazolium chloride 95/5.6 parts byweight), 1.0 part by weight of photo initiator Irgacure 1850, and 46parts by weight of 3,7-dimethyl-3-octanol were mixed and stirred. TheN/OH ratio of this composition was calculated and found to be 0.24. Themonomer mixture was degassed in argon atmosphere. In a globe box innitrogen atmosphere, two sheet of 100 μm thick “Parafilm” cut out in thecentral portions, were held as spacers between two 3 mm thick 10 cmsquare glass sheets (a gummed aluminum sheet was stuck to one of theglass sheets, to facilitate releasing), and the monomer mixture waspoured into there and polymerized in the space between the sheets bylight irradiation (Toshiba FLED fluorescent lamp, 8.4 kiloluxes, 15minutes), to obtain a sample film of a medical antimicrobialcomposition.

The sample films obtained as described above were exposed to ultrasonicwaves in water for 20 minutes, released from the glass sheets, immersedin 60 wt % 2-propanol aqueous solution at 60° C. overnight, furtherimmersed in 80 wt % 2-propanol aqueous solution at 60° C. for 2 hours,to extract impurities such as the remaining monomers, then beingimmersed in 50 wt % 2-propanol aqueous solution, 25 wt % 2-propanolaqueous solution and water lowered stepwise in IPA concentration oneafter another for minutes each, to be hydrated. The sample films wereimmersed in a boric acid buffer (pH 7.1 to 7.3) in a 200 mL glassbottle, and the glass bottle was placed in an autoclave for boilingtreatment at 121° C. for 30 minutes. The sample films were allowed tocool and subsequently taken out of the glass bottle, then being immersedin a boric acid buffer (pH 7.1 to 7.3). The obtained sample films weretransparent and free from turbidity, being excellent in appearancequality. Further, when the sample films were touched by a finger forconfirmation, they were found to be flexible, and when they were folded,they were not broken, being found to be excellent in mechanicalproperties. The obtained sample films were cut into 3 cm square samplefilms for evaluation of antimicrobial activity.

The sample film was dried in vacuum at 40° C. for 16 hours, and 2 g ofit was taken, ultrasonically washed in distilled water for 30 minutes,then immersed in 2-propanol, and heated at 60° C. for 24 hours. From theextract, the solvent was distilled away using an evaporator, and avacuum pump was used for reducing the pressure, to perfectly remove theremaining solvent. The extract was weighed and found to be 56.8 mg.Further, in reference to the infrared absorption spectrum, the extractwas found to be N-vinylpyrrolidone/vinylmethylimidazolium chloridecopolymer. From the result, it could be confirmed that the ammoniumgroup-containing polymer compound had been dispersed in theaforementioned sample film.

Synthesis Example 1

Into a 50 mL eggplant type flask, 4.71 g (50 mmol) of N-vinylimidazole,12.01 g (50 mmol) of n-octyl iodide and 0.1672 g of2,6-di-t-butyl-4-methylphenol (BHT) were added and heated at 65° C. for4 hours. After completion of reaction, the reaction product was purifiedusing a column packed with 90 g of silica gel, using 360 mL ofchloroform/methanol=50/1, 360 mL of chloroform/methanol=30/1, 360 mL ofchloroform/methanol=20/1, 180 mL of chloroform/methanol=10/1 and 180 mLof chloroform/methanol=5/1 in this order as eluents. Thin layerchromatography was performed to collect fractions containing theintended spot, and an evaporator was used to distill away the solvent,for obtaining a yellow oily ammonium salt monomer represented by thefollowing formula (x1).

Synthesis Example 2

One gram of the monomer represented by formula (x1) obtained in theabovementioned Synthesis Example 1, 1 g of 3,7-dimethyl-3-octanol and0.02 g of photo initiator Irgacure 1850 were mixed and stirred. Themonomer mixture was degassed in argon atmosphere, and poured into alaboratory dish with a diameter of 5 cm in a globe box in nitrogenatmosphere. It was irradiated with light (Toshiba FLED fluorescent lamp,8.4 kiloluxes, 15 minutes) and subsequently dissolved into an amount assmall as possible of methanol, and the solution was added dropwise into500 mL of ethyl acetate with stirring. The mixture was allowed to standat 5° C. for 3 hours. It was filtered, to obtain a solid that was washedwith a small amount of ethyl acetate. The pressure was reduced in adesiccator to distill away the solvent, for obtainingpoly(vinyloctylimidazolium iodide) as the homopolymer of the monomerrepresented by the abovementioned formula (x1).

Working Example 2

Polymerization and post-processing were performed as described forWorking Example 1, to obtain sample films for evaluation ofantimicrobial activity, except that the monomer composition used was amixture consisting of 22 parts by weight of the siloxanyl compoundrepresented by formula (y1), 36 parts by weight of the siloxanylcompound represented by the following formula (y3)

28 parts by weight of N,N-dimethylacrylamide, 8 parts by weight ofpolyvinylpyrrolidone (K-90), 12 parts by weight of 2-hydroxyethylmethacrylate, 1 part by weight of tri(ethylene glycol)dimethacrylate, 1part by weight of polydimethylsiloxane methacrylated at both the ends(X-22-164A produced by Shin-Etsu Chemical Co., Ltd.), 3.7 parts byweight of poly(vinyloctylimidazolium iodide) obtained in theabovementioned Synthesis Example 2, 1 part by weight of photo initiatorIrgacure 1850 and 14 parts by weight of 3,7-dimethyl-3-octanol. Theobtained sample films were transparent and free from turbidity, beingexcellent in appearance quality. Further, the sample films were touchedby a finger for confirmation, and were found to be flexible. Further,when they were folded, they were not broken, being found to be excellentin mechanical properties.

Working Examples 3 and 4

Polymerization and post-processing were performed according to themethod of Working Example 2, to obtain sample films for evaluation ofantimicrobial activity, except that the amount ofpoly(vinyloctylimidazolium iodide) used was changed as shown in Table 1.The obtained sample films were transparent and free from turbidity,being excellent in appearance quality. Furthermore, the samples weretouched by a finger for confirmation and found to be flexible. When theywere folded, they were not broken, being found to be excellent inmechanical properties.

TABLE 1 Amount of poly (vinyloctylimidazolium iodide) used (parts byweight) N/OH ratio Working Example 2 3.7 0.05 Working Example 3 5.0 0.07Working Example 4 10.0 0.14

Comparative Example 1

Sample films were obtained as described for Working Example 1, exceptthat the polymer compound was not added to the monomer mixture. Theywere cut into 3 cm square sample films for evaluation of antimicrobialactivity.

The sample obtained in Comparative Example 1 was dried in vacuum at 40°C. for 16 hours, and subsequently 2 g of it was taken and ultrasonicallywashed in distilled water for 30 minutes, then being immersed in2-propanol and heated at 60° C. for 24 hours. An evaporator was used todistill away the solvent from the extract, and further a vacuum pump wasused to reduce the pressure, for perfectly removing the remainingsolvent. The extract was weighed and found to be 0.1 mg. Further, thesolvent was changed to methanol, ethanol, toluene, hexane, acetone,methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofuran ordimethyl sulfoxide, to perform extraction, but in any of the cases, noextract in an amount corresponding to 0.1 wt % or more of the dry weightof the sample could be obtained.

Comparative Example 2

The sample films obtained in Comparative Example 1 were placed in a 50mL screw tube, and immersed in 1.7% PVP/polymethylvinylimidazoliumchloride (95/5) aqueous solution at room temperature for 16 hours.

Evaluation of Antimicrobial Activity

Three sample films were prepared in each of Working Examples 1 to 4, andPseudomonas aeruginosa NBRC 13275, one of typical bacteria observed inthe use of contact lenses, was inoculated into the sample filmsaccording to 5.2 Test Method for Plastic Products, Etc. of JIS Z2801:2000 “Antimicrobial Activity Test Methods and Antimicrobial Effectsof Antimicrobially Processed Products.” Immediately after theinoculation, the plate counts (initial plate counts) were determined,and after 24 hours at 35° C., the plate counts were determined forevaluation of antimicrobial activity. The results are shown in Tables 2and 3. The sample films obtained in Comparative Example 1 in whichpolymerization was performed without the polymer compound showedproliferation compared with the initial counts. The sample filmsobtained in Working Example 1 showed plate counts smaller by one digitthan the initial counts, and those obtained in Working Examples 2 to 4showed plate counts smaller by five digits than the initial counts,showing sufficient antimicrobial activity.

TABLE 2 Test 1 Test 2 Test 3 Mean Initial plate 2.72 × 10⁵ 2.64 × 10⁵2.33 × 10⁵ 2.6 × 10⁵ count Working Example 1 4.62 × 10⁴ 4.23 × 10⁴ 3.45× 10⁴ 4.1 × 10⁴ Comparative 6.26 × 10⁶ 6.90 × 10⁶ 6.41 × 10⁶ 6.5 × 10⁶Example 1

TABLE 3 Test 1 Test 2 Test 3 Mean Initial plate 3.15 × 10⁵ 3.45 × 10⁵3.60 × 10⁵ 3.4 × 10⁵ count Working Example 2 <10 <10 <10 <10 WorkingExample 4 <10 <10 <10 <10 Working Example 4 <10 <10 <10 <10Evaluation of Antimicrobial Activity after Ultrasonic Washing

The sample films obtained in Working Example 1 and Comparative Example 2were immersed in 300 mL of distilled water and ultrasonically washed for15 minutes, then being taken out for performing evaluation ofantimicrobial activity as described above. The results are shown inTable 4. The sample films obtained in Comparative Example 2, which wereimmersed in an antimicrobial polymer aqueous solution only lostantimicrobial activity and showed the proliferation of the bacterium,but the sample films obtained in Working Example 1 showed sufficientantimicrobial activity still after ultrasonic washing.

The sample film obtained in Comparative Example 2 was dried in vacuum at40° C. for 16 hours, and then 2 g of it was taken and ultrasonicallywashed in distilled water for 30 minutes, then being immersed in2-propanol and heated at 60° C. for 24 hours. An evaporator was used todistill away the solvent from the extract, and further a vacuum pump wasused to reduce the pressure, for perfectly removing the remainingsolvent. The extract was weighed and found to be 0.3 mg. Further, thesolvent was changed to methanol, ethanol, toluene, hexane, acetone,methyl ethyl ketone, ethyl acetate, butyl acetate, tetrahydrofuran ordimethyl sulfoxide, to perform extraction, but in any of the cases, noextract in an amount corresponding to 0.1 wt % or more of the dry weightof the sample could be obtained.

TABLE 4 Test 1 Test 2 Test 3 Mean Initial plate 2.55 × 10⁵ 2.87 × 10⁵2.96 × 10⁵ 2.8 × 10⁵ count Working Example 1 1.99 × 10³ 1.87 × 10³ 2.45× 10³ 2.1 × 10³ Comparative 5.74 × 10⁶ 5.23 × 10⁶ 5.56 × 10⁶ 5.5 × 10⁶Example 2

Working Examples 5 to 12

Polymerization and post-processing were performed as described forWorking Example 1, to obtain sample films for evaluation ofantimicrobial activity, except that the monomer composition was changedto a mixture consisting of w₁ parts by weight of the siloxanyl compoundrepresented by formula (y1), w₂ parts by weight of the siloxanylcompound represented by formula (y3), w₃ parts by weight of thepolydimethylsiloxane methacrylated at one end represented by formula(y2) (“Silaplane” FM-0711 produced by Chisso Corporation, weight averageweight about 1,000), w₄ parts by weightmethacryloxypropyltris(trimethylsiloxy)silane, V₁ parts by weight ofN,N-dimethylacrylamide, 8 parts by weight of polyvinylpyrrolidone(K-90), V₂ parts by weight of 2-hydroxyethyl methacrylate, 1 part byweight of tri(ethylene glycol)dimethacrylate, 1 part by weight ofpolydimethylsiloxane methacrylated at both the ends (X-22-164A producedby Shin-Etsu Chemical Co., Ltd.), U parts by weight of thepoly(vinyloctylimidazolium iodide) obtained in the abovementionedSynthesis Example 2, 2 parts by weight of photo initiator Irgacure 1850and 18 parts by weight of 3,7-dimethyl-3-octanol. The evaluation resultsof antimicrobial activity and the evaluation results of visualtransparency of the obtained sample films are shown in Table 5. Forcomparison, the results of Working Example 2 are also shown in Table 5.

TABLE 5 Anti- N/OH microbial w₁ w₂ w₃ w₄ V₁ V₂ U ratio activityTransparency Working 22 36 0 0 28 12 3.7 0.05 Count Transparent Example2 smaller by 5 digits Working 22 36 0 0 28 12 10 0.15 Count TransparentExample 5 smaller by 5 digits Working 22 36 0 0 28 12 20 0.29 CountTransparent Example 6 smaller by 5 digits Working 22 36 0 0 28 12 300.44 Count Moderately Example 7 smaller by turbid 5 digits Working 22 360 0 28 12 40 0.59 Count Highly Example 8 smaller by turbid 5 digitsWorking 22 36 0 0 28 12 0.37 0.005 Count Transparent Example 9 smallerby 1 digit Working 22 36 0 0 28 12 0.8 0.012 Count Transparent Examplesmaller by 10 3 digits Working 0 0 22 36 28 12 3.7 0.12 Count ModeratelyExample smaller by turbid 11 5 digits Working 0 0 22 36 33 7 10 0.56Count Highly Example smaller by turbid 12 5 digits w₁: Siloxanylcompound represented by formula (y1) (parts by weight) w₂: Siloxanylcompound represented by formula (y3) (parts by weight) w₃: Siloxanylcompound represented by formula (y2) (parts by weight) w₄:Methacryloxypropyltris(trimethylsiloxy)silane (parts by weight) V₁:N,N-dimethylacrylamide (parts by weight) V₂: 2-hydroxyethyl methacrylate(parts by weight) U: Poly(vinyloctylimidazolium iodide) (parts byweight)

Working Example 13

Polymerization and post-processing were performed according to themethod of Working Example 2, to obtain sample films for evaluation ofantimicrobial activity, except that the same amount ofpoly(N-methacryloxyethyl-N,N-dimethyl-N-butylammonium iodide) was usedinstead of poly(vinyloctylimidazolium iodide). The obtained sample filmswere somewhat turbid and inferior to the sample films obtained inWorking Example 2 in view of transparency. The count as the evaluationresult of antimicrobial activity was smaller by four digits.

Working Example 14

A monomer mixture consisting of 23 parts by weight of the siloxanylcompound represented by formula (y1), 35 parts by weight of thesiloxanyl compound represented by formula (y3), 28 parts by weight ofN,N-dimethylacrylamide, 8 parts by weight of polyvinylpyrrolidone(K-90), 12 parts by weight of 2-hydroxyethyl methacrylate, 1 part byweight of tri(ethylene glycol)dimethacrylate, 1 part by weight ofpolydimethylsiloxane methacrylated at both the ends (X-22-164A producedby Shin-Etsu Chemical Co., Ltd.), 3.7 parts by weight ofpoly(vinyloctylimidazolium iodide), 2 parts by weight of photo initiatorIrgacure 1850 and 18 parts by weight of 3,7-dimethyl-3-octanol wasdegassed in argon atmosphere.

An urethra catheter made of a silicone resin was irradiated with an highfrequency output of 40 W at an argon gas flow rate of 100 ml/min in aplasma reactor for 5 minutes. It was immediately immersed in theaforementioned monomer mixture in nitrogen atmosphere, and the monomermixture was polymerized by light irradiation (Toshiba FLED fluorescentlamp, 8.4 kiloluxes, 15 minutes), to obtain an urethra catheter coveredwith a medical antimicrobial composition.

The obtained urethra catheter was exposed to ultrasonic waves in waterfor 20 minutes and immersed in 60% IPA aqueous solution at 60° C.overnight, further immersed in 80% IPA aqueous solution at 60° C. for 2hours, to extract impurities such as the remaining monomers, andimmersed in 50% IPA aqueous solution, 25% IPA aqueous solution and waterlowered stepwise in IPA concentration one after another for about 30minutes each, to be hydrated. Finally, it was immersed in a boric acidbuffer (pH 7.1 to 7.3).

Working Example 15

An infusion tube covered with a medical antimicrobial composition wasobtained as described for Working Example 14, except that a tube (outerdiameter 15 mm, inner diameter mm, length 30 cm) made of a siliconeresin was used instead of the urethra catheter made of a silicone resin.

Synthesis Example 3

One gram of the monomer represented by formula (x2), 1 g of3,7-dimethyl-3-octanol and 0.02 g of photo initiator Irgacure 1850 weremixed and stirred. The monomer mixture was degassed in argon atmosphere,and poured into a laboratory dish with a diameter of 5 cm in a globe boxin nitrogen atmosphere. It was irradiated with light (Toshiba FLEDfluorescent lamp, 8.4 kiloluxes, 15 minutes), and subsequently dissolvedinto an amount as small as possible of methanol, and the solution wasadded dropwise into 500 mL of ethyl acetate with stirring. Then themixture was allowed to stand at 5° C. for 3 hours, and filtered, toobtain a solid that was washed with a small amount of ethyl acetate. Thepressure was reduced in a desiccator to distill away the solvent, forobtaining the homopolymer of the monomer represented by theabovementioned formula (x2).

Working Example 16

Polymerization and post-processing were performed according to themethod of Working Example 2, to obtain sample films, except that thehomopolymer of the monomer represented by formula (x2) obtained in theaforementioned Synthesis Example 3 was used instead ofpoly(vinyloctylimidazolium iodide). The obtained sample films weretransparent and free from turbidity, being excellent in appearancequality. Further, the sample films were touched by a finger forconfirmation, and found to be flexible. When they were folded, they werenot broken, being found to be excellent in mechanical properties.

Comparative Example 3

Twenty eight point eight parts by weight of the siloxanyl compoundrepresented by formula (y1), 35.5 parts by weight ofN,N-dimethylacrylamide, 26.8 parts by weight of the polydimethylsiloxanemethacrylated at one end represented by formula (y2) (“Silaplane”FM-0711 produced by Chisso Corporation, weight average molecular weightabout 1,000), 3.8 parts by weight of 2-hydroxyethyl methacrylate, 3.0parts of tri(ethylene glycol)dimethacrylate, 10 parts by weight of thecompound represented by the following formula (x3)

1.0 part by weight of photo initiator Irgacure 1850 and 46 parts byweight of 3,7-dimethyl-3-octanol were mixed and stirred. The N/OH ratioof this composition was calculated and found to be 0.24. The monomermixture was degassed in argon atmosphere. In a globe box in nitrogenatmosphere, two 100 μm thick Parafilms cut out in the central portionswere held as spacers between two 3 mm thick 10 cm square glass sheets(an aluminum seal was stuck to one of the glass sheets, to facilitatereleasing), and the monomer mixture was poured into there andpolymerized in the space between the sheets by light irradiation(Toshiba FLED fluorescent lamp, 8.4 kiloluxes, 15 minutes), to obtain asample film of a medical antimicrobial composition.

The sample films obtained as described above were immersed in 0.1Msodium hydroxide aqueous solution (40° C.) for 3 hours, to proceed withpolycondensation. Then, they were exposed to ultrasonic waves in waterfor 20 minutes, and peeled from the glass sheets, being immersed in 60wt % 2-propanol aqueous solution at 60° C., and further immersed in 80wt % 2-propanol aqueous solution at 60° C. for 2 hours, to extractimpurities such as the remaining monomers, then being immersed in 50 wt% 2-propanol aqueous solution, 25 wt % 2-propanol aqueous solution andwater lowered stepwise in IPA concentration one after another for about30 minutes each, to be hydrated. The sample films were immersed in aboric acid buffer (pH 7.1 to 7.3) in a 200 mL glass bottle, and theglass bottle was placed in an autoclave, to perform boiling treatment at121° C. for 30 minutes. After the sample films were allowed to cool,they were taken out of the glass bottle, and immersed in a boric acidbuffer (pH 7.1 to 7.3). The obtained sample films were white turbid andwere poor in appearance quality. Further, when the sample films weretouched by a finger for confirmation, they were rather hard and poor inflexibility, and when they were folded, some were broken and found to beinsufficient in mechanical properties.

The medical antimicrobial composition in an embodiment of this inventionis suitable for medical uses as various drugs, medical adhesives, woundcovering agents and medical devices, above all suitable for medicaldevices. Among medical devices, the medical antimicrobial composition issuitable for molded articles at least partially formed of a siliconeresin. Further, the medical antimicrobial composition is especiallysuitable for medical devices at least partially having a form selectedfrom a tube and a thin rod. Examples of the medical devices include anendoscope, catheter, infusion tube (including a gastrostomy tube), gastransfer tube, stent, sheath, cuff, tube connector, access port, drainbag and blood circuit.

1. A medical antimicrobial composition comprising an ammoniumgroup-containing polymer compound dispersed in a siloxanylstructure-containing polymer, wherein if the number of hydroxyl groupsbonded to the carbon atoms in the medical antimicrobial composition isOH and the number of ammonium nitrogens is N, then N/OH ratio is 0.001to 0.5.
 2. A medical antimicrobial composition, according to claim 1,wherein 30% or more of the silicon atoms in the medical antimicrobialcomposition are silicon atoms derived from a polar siloxanyl monomer. 3.A medical antimicrobial composition, according to claim 1, wherein atleast one component of the siloxanyl structure-containing polymer has astructure obtained from the siloxanyl monomer represented by thefollowing general formula (a):M-L-Sx  (a) where M denotes a radical polymerizable group; L denotes asubstituted or non-substituted divalent organic group with 1 to 20carbon atoms; and Sx denotes a siloxanyl group.
 4. A medicalantimicrobial composition, according to claim 3, wherein the L informula (a) denotes either of the groups represented by the followinggeneral formulae (b) and (c):

where j denotes an integer of 1 to 20; k denotes an integer of 1 to 6;and m denotes an integer of 1 to 17; subject to 3k+m≦20.
 5. A medicalantimicrobial composition, according to claim 4, wherein the L informula (a) denotes a group represented by the general formula (c).
 6. Amedical antimicrobial composition, according to claim 3, wherein atleast one component of the siloxanyl monomer is a polar siloxanylmonomer selected from the group consisting of the groups represented bythe following formulae (e) and (g):

wherein formula (g), Q denotes an alkyl group with 1 to 8 carbon atoms;and p denotes an integer of 1 to
 20. 7. A medical antimicrobialcomposition, according to claim 1, wherein the ammonium group-containingpolymer compound has a structure obtained from the ammonium salt monomerrepresented by the following general formula (f):

where R¹ denotes a substituted or non-substituted alkyl group with 1 to30 carbon atoms; R² to R⁷ denote, respectively independently, asubstituent group selected from hydrogen, substituted or non-substitutedalkyl group with 1 to 20 carbon atoms, and substituted ornon-substituted aryl group with 6 to 20 carbon atoms; R² and R³ may alsoform a ring; and X⁻ denotes a given anion.
 8. A medical antimicrobialcomposition, according to claim 1, which is obtained by polymerizing themonomers and/or macromonomers constituting the siloxanylstructure-containing polymer in a state of being mixed with the ammoniumgroup-containing polymer compound.
 9. A medical device comprising themedical antimicrobial composition as set forth in claim
 1. 10. A medicaldevice at least partially covered with the medical antimicrobialcomposition as set forth in claim
 1. 11. A medical device, according toclaim 9, which is a molded article containing a silicone resin.
 12. Amedical device, according to claim 9, which has a form selected from atube and a fine rod.
 13. A medical device, according to claim 12, whichis one selected from the group consisting of an endoscope, a catheter,an infusion tube, a gas transfer tube, a stent, a sheath, a cuff, a tubeconnector, an access port, a drain bag and a blood circuit.
 14. Amedical device, according to claim 12, which is a gastrostomy tube. 15.A medical antimicrobial composition according to claim 1, wherein theammonium group-containing polymer compound is present in a concentrationof between 0.1 to 30%.